STOJ FLS Lectures

Pathology

branch of medicine that deals with the lab examination of samples of body tissue for diagnostic or forensic purposes. Scientific foundation for all medicine

Anatomic pathology

study of organs and tissues

Clinical Pathology

study of bodily fluids

Molecular pathology

study of DNA/RNA

Disease

structural or functional disorder that produces signs or symptoms or affects a specific location

Etiology

Cause of the disease. Genetic or acquired.

Pathogenesis

Sequence of cellular, biochemical, molecular events following exposure to injurious agents.

Morphologic changes

Structural alterations in cells/tissues characteristic of disease or diagnostic of etiologic process. Basis for role of biopsy and microscopic evaluation of excised tissue in clinical care

Clinical manifestations

signs/symptoms, clinical course and outcome of the disease. Virtually all diseases begin with molecular or structural alteration inc all that ultimately determines ___

Signs

objective/measurable findings

Symptoms

Subjective findings

Homeostasis

normal cells handle physiologic demands within a steady state

Adaptations

reversible function/structural responses to changes or stresses

Cell injury

occurs in response to:
limits of adaptive responses exceeded
exposed to injurious agents or stress
deprived of essential nutrients
compromised by genetic mutations

Hypertrophy

increase in cell size. results in increased production in cellular proteins and increased organ size. no new cells. results in growth of organ size

Hyperplasia

increase in the number of cells when stimulus is applied.

Atrophy

Reduction in tissue or organ size due to decrease in cell size and number.

Authophagy

starved cell eating its own contents. Physiologic turnover of organelles. Clearance of intracellular aggregates accumulating during aging, stress, or various disease states

metaplasia

reversible change where one differentiated cell type is replaced by another. better suited for the environment and also changes stem cells

hypoxia

oxygen deprivation. most important cause of cell injury

Apoptosis and necrosis

two principal pathways of cell death.

necrosis

pattern of cell death that leads to denaturation of intracellular enzymes and loss of membrane integrity. Cells are digested by lysosomal enzymes within the cell that are recruited by leukocytes

Coagulative necrosis

architecture of dead tissues and cells preserved for at least a few days.

infarct

localized areas of coagulative necrosis

liquefactive necrosis

enzymatic digestion of dead cells resulting in liquid viscous mass. often seen following brain infarcts

Gangrenous necrosis

clinical term denoting necrosis of multiple tissue planes
superimposed bacterial infection results in more liquefactive necrosis

Caseous necrosis

cheese like, often seen in context of TB, associated with distinctive pattern of inflammation termed granuloma

Fibrinoid necrosis

usually seen in immune reactions involving blood vessels (vasculitis). Ag-Ab complexes deposit in walls of arteries together with extravasated fibrin

ATP Delpletion

Reduced supply of oxygen and nutrients, mitochondrial damage and toxins result in this fundamental cause of necrotic cell death

Mitochondrial damage

consequences of this result in formation of permeability of transition pores, loss of membrane conductance, and leakage of pro-apoptotic protiens

Intracellular Ca2+

increased__ can cause cell death by: accumulating within mitochondria and opening mitochondrial permeability transition pores, activating potentially deleterious intracellular enzymes, directly inducing apoptosis

Free radicals

molecule with single unpaired electron in outer orbit. highly reactive, attacks adjacent molecules. important mechanisms of cell damage

oxidative stress

oxygen derived free radicals have increased production during cellular respiration and decreased removal by cellular defense systems. Part of routine inflammation and is implicated in pathologic processes including cancer, aging, alzheimers

damaged membranes

can cause leakage of intracellular proteins into circulation providing means of detecting tissue-specific cellular injury

Ischemia

inadequate blood supply to organ or body part
Most common cause of cell injury in clinical medicine

Hypoxia

deficiency in oxygen reaching the tissues

reperfusion of ischemic tissues

can paradoxically exacerbate cell injury and cause death. contributes to tissue damage during management of myocardial and cerebral infarctions.

Chemical (toxic) injury

frequent problem in clinical medicine. Major limit to drug therapy because liver is frequent target of drug toxicity due to number of drugs metabolized there.

Apoptosis

programmed cell death/suicide. intrinsic enzymes degrading cell DNA and proteins. For cells physiologically destined to die

apoptosis 2 pathways

mitochondrial (intrinsic) and death receptor (extrinsic)

Caspases

enzymes that result in the activation of apoptosis

Mitochondrial

apoptosis major pathway in mammalian cells

BCL2

family of proteins that balance apoptosis on outer mitochondrial membrane

TNFR, Fas

activation factors of death receptor pathway

Tp53 gene

tumor suppressor gene that encodes for apoptosis if damage to cell is high

unfolded protein response

cytoprotective response that increases ER chaperone protein production, enhanced proteosomal destruction of misfolded proteins, and slowed protein translation

ER stress

activation of caspases leads to apoptosis, a common feature of neurodegenerative diseases

Necroptosis

form of cell death resembling apoptosis mechanistically and necrosis morphologically. plasma membrane rupture, cell swelling, ROS generation, NO caspase activation

triglycerides

Main constituents of natural fats and oils
Conversion product of calories not immediately used

Cholesterol

Important constituent of cell membranes and some steroids/hormones
High blood levels associated with increased saturated fat intake

Phospholipids

lipid major component of cell membranes

Steatosis

Abnormal intracellular accumulation of triglycerides
Often seen in liver and from alcohol abuse

Atherosclerosis

Intracellular cholesterol accumulation within intimal layer of aorta and large arteries
Associated with hypercholesterolemia

Xanthomas

Intracellular cholesterol accumulations within skin and tendons
Associated with hypercholesterolemia

Anthracosis

blacking of lungs and lymph nodes from pulmonary macrophage eating of carbon

Dystrophic calcification

calcium deposition in dying tissues, not associated with hypercalcemia or any calcium metabolism

metastatic calcification

calcium deposition in normal tissues association with hypercalcemia

Warner syndrome

characterized by defective DNA helicase involved in DNA replication

Senescence

after limited capacity for replication and become arrested in terminally non-dividing state

telomerase

regulated telomere length

inflammation

response of vascularized tissues to infection and damage. used to eliminate offending agents. protective response for survival

blood

defense mediators like leukocytes, antibodies, and complement usually circulate in the

Leukocytes

monocytes, macrophages, lymphocytes, and granulocytes are all considered

granulocytes

neutrophils, eosinophils, and basophils are all considered

fever

common systemic manifestation of inflammation

local

inflammatory is usually a __ response to infection/tissue

termination

when the offending agent is eliminated

rubor

redness

tumor

swelling

calor

heat

dolor

pain

functio laesa

loss of function

triggers of inflammation

infections, tissue necrosis, foreign bodies, immune reactions

acute inflammation

initial, rapid response to infection. develops in minutes, last for hours or days, exudation of fluid/plasma proteins and emigration or leukocytes (neutrophils)

Chronic inflammation

Protracted phase of inflammation occurring if acute inflammation cannot clear offending agent
Of longer duration
Lymphocytes and macrophages major cell types
Associated with more tissue destruction and healing by deposition of connective tissue

acute inflammation components

dilation of small blood vessels
increased permeability of small blood vessels
emigration of leukocytes from microcirculation

exudation

escape of fluid, proteins, blood cells from vascular systems into interstitial tissues or body cavity

transudate

extravascular fluid with low protein content and little/no cellular debris

exudate

extravascular fluid with high protein content and cellular debris

pus

exudate rich in neutrophils, dead cell debris, microbes

vasodilation

induced by action of mediators like histamine on vascular smooth muscle. results in increased and slower blood flow

vascular leakage

increased vascular permeability

lymphadenitis

lymph nodes becoming secondarily inflamed

leukocytes

neutrophils and macrophages. capable of phagocytosis and produce growth factors that aid in repair.

chemokine

a cytokine with function of leukocyte recruitment

cytokine

messenger molecule of immune system

Margination

step 1 of leukocyte adhesion to activated endothelium, occurs during vasodilation

Rolling

step 1 of leukocyte adhesion. Period of transient attachment/detachment.

selectins

the family of proteins that mediates rolling.

adhesion

point at which a cell becomes firmly attached to vessel wall and cytoskeleton reorganizes and cells spread out onto endothelial surface

integrins

family of proteins that mediates adhesion

leukocyte adhesion deficiency

a defect in either integrins or selectin function that leads to increased vulnerability to bacterial infections

leukocyte transmigration

step 2 of leukocyte recruitment. occurs mainly in post-capillary venules,

leukocytes move towards site of injury by chemotaxis

step 3 of leukocyte recruitment. exogenous and endogenous agents act as chemoattractants

chemotaxis

locomotion along a chemical gradient

exogenous agent

bacterial products are known as

endogenous agent

cytokines, components of the complement system like C5a, and arachidonic acid metabolites are known as

neutrophils

what predominates first 6-24 hours in acute inflammation

macrophages

replace neutrophils for hours 24-48 in acute inflammation

phagocytosis

intracellular recognition and attachment of particle to be ingested.